Muscle protein brakes growth via mTOR pathway

When a muscle is stretched for an extended period, the body responds by making it longer. This process is called longitudinal hypertrophy. The key player is titin, the largest protein known to science. This enormous spring-like protein in muscle cells acts as a sensor for mechanical tension. When titin is stretched, it sends signals that prompt the muscle cell to adapt and grow.

In the new study, published in eLife and conducted in rats and mice, the researchers investigated which proteins help titin relay those signals. They found that muscle ankyrin repeat proteins (MARPs) play an inhibitory role. Mice lacking MARPs showed more longitudinal growth after mechanical stretch than normal mice.

mTOR: the switch

The increased growth in MARP-deficient mice turned out to run through mTORC1, a central regulator of cell growth and protein production. mTORC1 is also one of the most studied targets in longevity science: inhibiting it with rapamycin extends lifespan in multiple animal models. In this study, mTORC1 inhibition with rapamycin was used to suppress the enhanced growth in MARP-deficient mice. That confirms mTOR as the switch driving the increased longitudinal growth.

The finding illustrates how MARPs normally put a brake on mTOR-driven muscle growth, a balance that is likely functional: uncontrolled longitudinal growth could cause mechanical problems in the body.

Relevance for muscle maintenance in aging

Muscle loss with aging, known as sarcopenia, is one of the leading causes of lost independence in older adults. Understanding how muscle growth is regulated at the molecular level offers potential targets for future interventions. The role of titin and MARP proteins in this system was previously unknown. Whether this insight can eventually be translated into treatments in humans has not yet been studied and requires further evidence.

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